Patient cohort
From November 2019 to July 2021, we screened a total of 174 patients who were hospitalised or outpatients in the first ward of the Department of Cardiology of Beijing Anzhen Hospital due to ischemic symptoms and had confirmed nonobstructive coronary arteries by CCTA or ICA. The MPRI was achieved in 88 patients who underwent stress-perfusion CMR. Finally, 80 patients with an MPRI of < 2.5 were analysed.
The average age was 54 years (54 ± 14 years), and 66.3% were males. Forty-eight (60%) and 32 (40%) patients underwent CCTA and ICA, respectively, confirming the presence of nonobstructive coronary arteries. The flow chart in Fig. 1 provides further details.
Patient characteristics
The clinical characteristics of the patients are summarised in Table 1. Age (57.61 ± 9.65 vs. 51.74 ± 11.41) and presence of diabetes mellitus (45.5% vs. 21.3%) in the group with an MPRI of ≤ 1.47 were higher than the MPRI of > 1.47 group (P < 0.05). There were no significant differences in gender, being overweight, smoking, heart rate, blood pressure, myocardial infarction history, PCI history, hypertension, and hyperlipidaemia between the two groups (P > 0.05).
Table 1
|
MPRI ≤ 1.47
|
MPRI > 1.47
|
P value
|
N
|
33
|
47
|
|
Age
|
57.61 ± 9.65
|
51.74 ± 11.41
|
0.006*
|
Gender(male)
|
20(60.6%)
|
32(68.1%)
|
0.478
|
Overweight
|
23(69.7%)
|
30(63.8%)
|
0.637
|
Smoking
|
9(27.2%)
|
21(44.7%)
|
0.160
|
Vital signs
|
|
|
|
Heart rate
|
70.81 ± 6.92
|
71.89 ± 8.94
|
0.566
|
SBP
|
127.64 ± 12.88
|
128.20 ± 17.91
|
0.768
|
DBP
|
75.18 ± 7.56
|
78.20 ± 11.66
|
0.313
|
Comorbidity
|
|
|
|
MI history
|
4(12.1%)
|
5(10.6%)
|
0.837
|
PCI history
|
7(21.2%)
|
8(17.0%)
|
0.773
|
Hypertension
|
21(63.6%)
|
23(52.3%)
|
0.255
|
Dyslipidemia
|
17(51.5%)
|
25(53.2%)
|
0.883
|
Diabetes mellitus
|
15(45.5%)
|
10(21.3%)
|
0.022*
|
No risk factors
|
8(24.2%)
|
11(23.4%)
|
0.931
|
BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; MI, myocardial infarction; PCI, percutaneous coronary intervention. *p < 0.05 |
Table 2
|
MPRI ≤ 1.47
|
MPRI > 1.47
|
P value
|
WBC(×109 /L)
|
6.84 ± 1.97
|
6.80 ± 1.75
|
0.930
|
hs-CRP (mg/l)
|
0.64(0.34,4.33)
|
0.65(0.45,1.52)
|
0.832
|
C1q (mg/l)
|
146.19(130.10,157.19)
|
146.30(131.85,178.15)
|
0.804
|
NT-pro BNP (pg/ml)
|
60.30(29.05,78.60)
|
61.60(42.15,115.55)
|
0.945
|
CK-MB (ng/ml)
|
1.90(1.00,2.90)
|
1.70(1.50,2.10)
|
0.586
|
cTnI(ng/ml)
|
2.70(0.10,7.05)
|
2.70(0.22,5.25)
|
0.598
|
D-Dimer (ng/ml)
|
79.50(50.50,109.25)
|
54.00(30.50,81.00)
|
0.056
|
FBG (mmol/l)
|
6.33(5.16,8.01)
|
5.30(5.15.6.56)
|
0.035*
|
HbA1c (%)
|
6.30(5.70,7.70)
|
5.80(5.60,6.50)
|
0.004*
|
TC (mmol/l)
|
3.76 ± 0.84
|
3.88 ± 1.05
|
0.861
|
TG (mmol/l)
|
1.32(1.16,1.62)
|
1.26(0.98,1.51)
|
0.454
|
LDL-C (mmol/l)
|
2.11 ± 0.73
|
2.16 ± 0.85
|
0.870
|
HDL-C (mmol/l)
|
1.12 ± 0.25
|
1.14 ± 0.33
|
0.953
|
UA((µmol/L)
|
361.18 ± 106.619
|
303.38 ± 91.071
|
0.020*
|
HCY
|
11.85(10.30,15.10)
|
11.75(10.12,13.50)
|
0.413
|
Echocardiography
|
|
|
|
LVEF
|
59.94 ± 15.39
|
63.75 ± 6.95
|
0.476
|
E/A
|
0.95 ± 0.37
|
1.00 ± 0.33
|
0.449
|
LV diastolic dysfunction
|
20(90.9%)
|
16(69.6%)
|
0.135
|
WBC, white blood cells; hsCRP, high-sensitivity C-reactive protein; C1q, complement C1q; NT-pro BNP, NT- B type natriuretic peptide; CK-MB creatine kinase isoenzyme MB; cTnI, cardiac troponin I; FBG, fasting blood glucose;HbA1c, glycosylated hemoglobin; TC, total cholesterol;TG, triacylglycerol;LDL-C, Low Density Lipoprotein Cholesterol;HDL-C, High density lipoprotein cholesterol;UA, uric acid;HCY, Homocysteine; LVEF, left ventricular ejection fraction; LV, left ventricular. *p<0.05 |
Laboratory examination
FBG [6.33(5.16,8.01) vs. 5.30(5.15.6.56)], HbA1c [6.30(5.70,7.70) vs. 5.80(5.60,6.50)] and UA (361.18 ± 106.619 vs. 303.38 ± 91.071) in the group with an MPRI of > 1.47 were higher than the MPRI of ≤ 1.47 group. There were no significant differences in inflammatory indices (WBC, hs-CRP, and C1q), myocardial injury markers (NT-pro BNP, CK-MB, cTnI, and D-dimer), blood lipids (TC, TG, LDL-C, and HDL-C), HCY, and echocardiographic indices (LVEF, E/A, and LV diastolic dysfunction) between the two groups.
Symptoms and psychological assessment
There was no significant difference in the classification of angina (typical, exercise, rest, evening angina, and breathlessness) and the degree of angina (CCS classification and SAQ) between the two groups (Supplementary Table 1). There was also no significant difference in the PHQ-9 and GAD-7 scores (Supplementary Table 2).
Correlation analysis and logistic regression of MPRI with risk factors
In patients with CMD, the MPRI was negatively correlated with age (r=-0.349, P = 0.001), diabetes mellitus (r=-0.324, P = 0.003), HbA1c (r=-0.378, P = 0.004), UA (r = 0.311, P = 0.008), and HCY (r = 0.246, P = 0.048). The MPRI was not correlated with age, FBG, LVEF, E/A, PHQ-9, and GAD-7 (P > 0.05) (Supplementary Table 3). In patients with CMD without diabetes mellitus, only age (r=-0.335, P = 0.012) was negatively correlated with the MPRI. In CMD patients with diabetes mellitus, the MPRI did not correlate with the included risk factors (P > 0.05).
Tables 3 and 4 show the logistic regression analysis of the MPRI and risk factors. Due to the synergistic effect of diabetes mellitus and HbA1c, they were included in the logistic regression analysis, respectively. Logistic regression analysis showed that HbA1c (OR = 2.336, 95% CI: 1.119–4.876, P = 0.024) and diabetes mellitus (OR = 4.494, 95% CI: 1.225–16.485, P = 0.023) were independent risk factors for MPRI reduction in patients with CMD. For those without diabetes mellitus, HbA1c was still predictive of a decline in MPRI (OR = 19.953, 95% CI: 1.743–93.449, P = 0.029). However, in patients with diabetes mellitus, HbA1c could not predict a declined MPRI (OR = 0.984, 95% CI: 0.265–3.658, P = 0.981).
Table 3
Logistic regression analysis (including HbA1c)
Factor
|
ALL
|
|
Without diabetes mellitus
|
With diabetes mellitus
|
|
OR (95%CI)
|
P value
|
OR (95%CI)
|
P value
|
OR (95%CI)
|
P value
|
Gender(male)
|
2.032(0.411,10.035)
|
0.384
|
1.014(0.071,14.529)
|
0.992
|
0.448(0,6.462)
|
0.826
|
Age
|
1.020(0.929,1.119)
|
0.683
|
1.000(0.876,1.142)
|
0.999
|
1.105(0.884,1.381)
|
0.381
|
UA
|
0.992(0.981,1.003)
|
0.148
|
1.002(0.984,1.019)
|
0.863
|
0.984(0.957,1.011)
|
0.251
|
HCY
|
0.995(0.913,1.084)
|
0.902
|
0.985(0.865,1.121)
|
0.820
|
0.987(0.785,1.240)
|
0.910
|
PHQ-9
|
1.053(0.863,1.286)
|
0.611
|
1.081(0.817,1.431)
|
0.587
|
0.886(0.407,1.928)
|
0.886
|
GAD-7
|
1.030(0.849,1.248)
|
0.766
|
1.245(0.894,1.735)
|
0.195
|
1.259(0.597,2.654)
|
0.545
|
HbA1c
|
2.336(1.119,4.876)
|
0.024*
|
19.953(1.743,93.449)
|
0.029*
|
0.984(0.265,3.658)
|
0.981
|
UA, uric acid;HCY, Homocysteine; PHQ-9, Patient Health Questionnaire-9; GAD-7, Generalized Anxiety Disorder Questionnaire-7; FBG, fasting blood glucose; HbA1c, glycosylated hemoglobin; *p < 0.05 |
Table 4
Logistic regression analysis (including diabetes mellitus)
Factor
|
OR (95%CI)
|
P value
|
Gender(male)
|
1.316(0.328,5.285)
|
0.682
|
Age
|
1.013(0.948,1.082)
|
0.611
|
UA
|
0.993(0.984,1.002)
|
0.138
|
HCY
|
0.964(0.885,1.051)
|
0.403
|
PHQ-9
|
1.037(0.889,1.209)
|
0.646
|
GAD-7
|
0.996(0.846,1.172)
|
0.957
|
Diabetes mellitus
|
4.494(1.225,16.485)
|
0.023*
|
UA, uric acid;HCY, Homocysteine; PHQ-9, Patient Health Questionnaire-9; GAD-7, Generalized Anxiety Disorder Questionnaire-7; *p < 0.05 |